Pulmonary edema (“PE”) affects millions of people each year, causing substantial morbidity and mortality. In PE patients, the alveoli flood with liquid from pulmonary capillaries which compromises oxygen transfer to the systemic circulation (Hall, et al. in CURRENT THERAPY IN RESPIRATORY MEDICINE (R. Cherniack, Ed., 1986), pp. 222-227). This sequence of events results in hypoxemia, hypercapnia, and death if no corrective measures are taken.
Any condition or agent that disrupts fluid homeostasis in the lungs can result in PE, which can be broadly divided into cardiogenic and non-cardiogenic PE (see, e.g., Kakouros and Kakouros, Hellenic J. Cardiol. 44:385-391 (2003). For example, Acute Lung Injury/Adult (acute) Respiratory Distress Syndrome or “ARDS,” which can develop as a result of lung injury due to, e.g., pneumonia, septic shock, trauma, aspiration of vomit, or chemical inhalation, is often associated with non-cardiogenic PE. Non-cardiogenic PE is characterized by a change in the vascular permeability of the lung tissue which leads to an increase in fluid levels in the lungs. Cardiogenic PE is often caused by left sided heart failure and can be a complication of a heart attack, leaking or narrowed heart valves (mitral or aortic valves), or any disease of the heart that either results in weakening and/or stiffening of the heart muscle (cardiomyopathy). The failing heart transmits its increased pressure to the lung veins. As pressure in the lung veins rises, fluid is pushed into the air spaces (alveoli). This fluid then becomes a barrier to normal oxygen exchange, resulting in shortness of breath. Cardiogenic PE is characterized by increased capillary hydrostatic pressure which leads to an increase in fluid levels in the lungs.
PE is caused by, e.g., altered capillary permeability; infection; inhaled or circulating toxins; vasoactive substances (e.g., histamine, kinins); disseminated intravascular coagulation; immunologic reactions; radiation-associated pneumonia; uremia; near-drowning; smoke inhalation; and acute respiratory distress syndrome; left ventricular failure; mitral stenosis; bacterial endocarditis; pulmonary venous fibrosis; congenital stenosis of the origin of the pulmonary veins; pulmonary venoocclusive disease; overinfusion of fluids; hypoalbuminemia (e.g., from renal, hepatic, nutritional, or protein-losing enteropathy); high-altitude; drug overdoses, CNS trauma, subarachnoid bleeding, pulmonary embolism, pulmonary parenchymal disease, eclampsia, anesthesia, and cardiopulmonary bypass operations.
Symptoms of PE may include, for example, shortness of breath, rapid and/or labored breathing, tachycardia, hypertension, tightness in the chest, cold extremities with or without accompanying cyanosis, cough with a frothy or pink sputum, extensive use of accessory muscles of respiration, moist rales with or without wheezing, and combinations thereof. Tests to diagnose PE include blood tests such as complete blood count (CBC), blood urea nitrogen (BUN), creatinine, and serum protein. Urianalysis, arterial blood gases (ABGs), chest X-rays, and electrocardiograms (ECG) and all used to assist the physician in narrowing the diagnosis down to PE.
Treatment of cardiogenic PE typically involves placing the patient on 100% oxygen, morphine to ease anxiety and provide some beneficial cardiac effects, furosemide for diuresis, vasodilators to reduce the work against which the myocardium must pump, and inotropic drugs such as doputamine to increase cardiac contractility. Other measures that have been used are rotating tourniquets on three of four limbs and reducing blood volume by 500 ml.
Unfortunately, no specific or satisfactorily effective treatment for PE is available. Thus, there is a need in the art for more effective and specific therapies for PE. The present invention addresses this and other problems.